Significant impairment of humoral and cellular immunity occurs with age; to date, this has been demonstrated only in the intact organism or with functionally mature units of the immune system. The recent description of senescence in vivo of an antibody-forming cell clone makes clear the need for studies on stem cell populations throughout the life span of an organism in order to detect changes in the regenerative capacity of the immune system that may occur with age. It is proposed that in vitro culture methods be developed or improved to provide (1) a quantitative assay system for the precursors of IgM, IgG and IgA producing cells, (2) means to observe the interactions of B-cells and T-cells in normal maturation and in response to antigenic stimulation, (3) a quantitative assay for the precursors of the cells that mediate cellular immune responses, and (4) means to study the functional changes that occur in the precursors of T-cells during interaction with thymic stroma or its functional equivalent. Initially these studies will continue observations made on embryonic mouse tissues, and after the methods have been standardized, stem cell populations will be studied in young and aged mice.